Preparation of Chiral 2-(2-Bromobenzyl)-1,3-dioxolanes and Their Addition to Acylimines

Abstract

A series of enantiomerically pure 2-(2-bromobenzyl)-1,3-dioxolanes 10 has been prepared by transacetalization of the dimethyl acetal 8 or the enol ether 7 with enantiomerically pure C2 symmetric 1,2-diols. We investigated the ability of the chiral 1,3-dioxolane moiety to control the diastereoselectivity during the addition of the aryllithium intermediates 18 to the acylimines 17. Those reactive aryllithium species were generated by bromine/lithium exchange at the bromo acetals 10. In this series the best diastereoselectivity was obtained by addition of the aryllithium intermediate 18b to the acylimine 17a to yield the diastereomeric addition products 19c/20c in a ratio of 72:28. After separation, the main diastereomer 19c was cyclized to afford the dihydroisoquinoline (R)-21, which was then hydrogenated to give the NMDA antagonistic 1-phenyl-1,2,3,4-tetrahydroisoquinoline (R)-2. The chiral auxiliary, the diol 9b, cleaved during the cylization of 19c, could be recovered in 89% yield.